Download Parvovirus B19 Infections Pathogenesis

Parvovirus B19
Infections
Pathogenesis

Autonomous parvoviruses are highly parasitic because
of their molecular simplicity.

Parvovirus B19 replicates in mitotically active cells and
prefers cells of the erythroid lineage.

The human parvovirus B19 receptor has been
identified as globoside, the blood group “’P” antigen.

Major sites of replication have been assumed to be
adult marrow and fetal liver (sites of erythropoiesis).

The absence of lipid envelope and the small
DNA content contribute to the high heat
stability of parvoviruses.

B19 virus has been transmitted in pasteurized
blood products and the virus resists solvent
detergent treatment.

The major route of transmission is probably the
upper airway, but can be transmitted by
contaminated blood products and
transplacentally.

Spread is by viremia which starts at day 5 to 6
and peaks at 8 to 9 days.

High titers (1014/ml) are reached and virus is
released into oral and respiratory secretions.

Viremia is accompanied by nonspecific flu-like
symptoms.

Bone marrow suppression coincides with
viremia.

The illness is biphasic and the second phase
coincides with antibody production

Manifestations are immune- mediated mainly in
the form of skin rash, and joint involvement.

Virus is rarely detected in patients with fifth
disease because the clinical manifestations are
secondary to immune complex formation

Patients present to medical attention after the
period of viremia has passed.

Consistent pathologic changes have been restricted to
hematopietic tissue

Giant pronormoblasts, depletion of later erythroid
precursor cells and more occasionally dysplastic
changes in myeloid and megakaryocytic cells.

Protective, long- lasting antibody is produced.

Cessation of erythropoiesis lasts 5-7 days.

Cases of ITP and HSP have apparently followed acute
parvovirus infection.
Transient Aplastic Crisis

An abrupt cessation of red blood cell production in
the bone marrow in persons with underlying
hemolysis.

It is characterized by reticulocytopenia, absent
erythroid precursors in marrow, and precipitous
worsening of anemia.

Transient aplastic crisis results when failed
erythropoiesis is combined with a much shortened
red blood cell life span.

Although the illness is self – limited, the patient is
acutely ill.

Symptoms may include dyspnea, fatigue,
extreme lassitude, confusion, and congestive
heart failure.

The crisis can precipitate cerebrovascular
accidents in patients with sickle cell disease

Death can occur from profound anemia and
heart failure.

The anemia of TAC is readily treated by blood
transfusion. It is rarely complicated by bone
marrow necrosis.

TAC occurs in :
- Sickle cell disease
- Congenital erythrocyte membrane defects
- Enzymopathies
- Thalassemia
- Acquired hemolytic anemia in adults.
- Conditions of erythroid stress:
- hemorrhage and iron deficiency
- myelofibrosis
- after bone marrow transplantation.


It may be followed by pancytopenia with
hemophagocytosis.
TAC is often associated with variable degrees of
neutropenia and thrombocytopenia.
Persistent infection

Pure red cell aplasia.

Failure to mount a neutralizing antibody
response to the virus

No immune complex mediated symptoms of
fifth disease; fever, rash, and polyarthralgia/
polyarthritis.

Documented in four patient populations:
- Congenital immunodeficiency (Nezelof’’s
Syndrome)
- Children with lymphoblastic leukemia and
other malignancies in remission after or
during chemotherapy
- patients with AIDS
- Recipients of solid organ transplants.

Clinically, the anemia is severe, and the patient
becomes dependent on transfusions.

There may be intermittent neutropenia.

The bone marrow contains giant
pronormoblasts.

The anemia may be intermittent, with periods
of relapse and remission
Diagnosis

Virus Isolation

Human erythroid progenitors remain the most
convenient productive tissue culture system.

Bone marrow, peripheral blood, fetal liver, and a few
leukemic cells or cell lines have been used to
reproduce virus.

Serology

PCR
IgM and IgG.
most specific